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EC number: 204-524-2 | CAS number: 122-14-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 November 1990 - 10 December 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1990
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Fenitrothion
- EC Number:
- 204-524-2
- EC Name:
- Fenitrothion
- Cas Number:
- 122-14-5
- Molecular formula:
- C9H12NO5PS
- IUPAC Name:
- O,O-dimethyl O-3-methyl-4-nitrophenyl phosphorothioate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- Fenitrothion
Batch No.: 90617
Purity: 93.7%
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on species / strain selection:
- Standard species/strain used for regulatory studies
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Kitayama Labs, Japan
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 1944-2311 g (males), 1704-2026 g (females)
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26
- Humidity (%): 45-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 15 November 1990 To: 10 December 1990
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TEST SITE
- Area of exposure: 12x14 cm
- Type of wrap if used: occlusive
REMOVAL OF TEST SUBSTANCE
- Washing (if done): water and soap
- Time after start of exposure: 6 hours
VEHICLE
- Justification for use and choice of vehicle: undiluted
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 6 hours/day for 21 successive days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- control (distilled water)
- Dose / conc.:
- 3 mg/kg bw/day
- Dose / conc.:
- 10 mg/kg bw/day
- Dose / conc.:
- 50 mg/kg bw/day
- Dose / conc.:
- 250 mg/kg bw/day
- No. of animals per sex per dose:
- 5/sex
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Fenitrothion was administered percutaneously to groups of 5 male and 5 female New Zealand White rabbits at the dose levels of 0, 3, 10, 50 and 250 mg/kg bw/d by the topical route for a period of 21 successive days. The test material, a brown oily substance, was administered undiluted. The control group received distilled water.
- Positive control:
- Not required
Examinations
- Observations and examinations performed and frequency:
- Parameters evaluated were clinical observations (twice daily), dermal reactions (daily), body weights and food consumption (weekly), plasma and erythrocyte cholinesterase activity (one week before treatment, 2 and 24 hours after final dosing), haematology and biochemistry.
- Sacrifice and pathology:
- Brain cholinesterase activity, necropsy, organ weights and histopathology were assessed at study termination.
- Statistics:
- Parameters measured in this study were assessed and compared using appropriate statisitcal methods.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Signs observed in animals prior to death were hypoactivity, muscular hypotonia, tremor, bradypnoea, hypothermia, salivation, clonic convulsion, loose or mucous stool, diarrhea and soiled perineum. In the surviving three females at 250 mg/kg bw/d, one animal revealed loose stool and soiled perineum and the other two animals showed no abnormalities. No clinical signs were noted in animals of the control and 3, 10 and 50 mg/kg bw/d groups.
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- Very slight or well defined erythema and very slight or slight oedema were observed at the application site in males and females of the 3, 10 and 50 mg/kg bw/d groups, and were classified as mild according to the Draize index. Males and females of the 250 mg/kg bw/d group showed slightly more severe irritation than other treated groups. The maximum mean irritation scores at 250 mg/kg bw/d were classified as moderate according to the Draize index. The other dermal reaction observed in all groups treated with fenitrothion was desquamation of the epidermis.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Five males and two females at 250 mg/kg bw/d showed deterioration of general condition and died during the administration period (two males and one female were killed in a moribund condition).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Depression of body weight gain and decrease in body weights were observed in males and females at 250 mg/kg bw/d.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased WBC count and variable differential counts were observed in decedents at 250 mg/kg bw/d. No haematological effects were reported at lower dose levels.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased AST and ALT activity and blood urea nitrogen and a decrease in serum electrocytes were observed in some animals at 250 mg/kg bw/d. No effects on clinical chemistry parameters were reported at lower dose levels.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased adrenal weight was seen in some rabbits at 250 mg/kg bw/d.
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- At 250 mg/kg bw/d, one male and one female revealed slight focal necrosis in the liver; histopathological changes in the digestive tract and kidney were considered to reflect a general deterioration of condition.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Erythrocyte cholinesterase activity decreased in males and females at 10, 50 and 250 mg/kg bw/d. Plasma and brain cholinesterase activities decreased in males at 50 and 250 mg/kg bw/d and in females at 10, 50 and 250 mg/kg bw/d. No significant changes in erythrocyte, plasma or brain cholinesterase activities were observed at 3 mg/kg bw/d.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- < 3 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Local dermal irritation
- Remarks on result:
- other: Local toxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 3 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: cholinesterase activity
- Remarks on result:
- other: Systemic toxicity
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 10 mg/kg bw/day
- System:
- nervous system
- Organ:
- brain
- neurons
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Any other information on results incl. tables
Summary of dermal reactions (males)
3 mg/kg bw/d |
10 mg/kg bw/d |
50 mg/kg bw/d |
250 mg/kg bw/d |
|||||||||
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
|
Day 0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 4 |
0 |
0 |
0 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
0.20 |
0 |
0.20 |
Day 5 |
0 |
0 |
0 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
0.40 |
0 |
0.40 |
Day 6 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
0.40 |
0 |
0.40 |
0.60 |
0 |
0.60 |
Day 7 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
0.80 |
0 |
0.80 |
1.20 |
0.20 |
1.40 |
Day 8 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0.20 |
1.20 |
1.25 |
1.00 |
2.25 |
Day 9 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.20 |
0.20 |
1.40 |
1.33 |
1.33 |
2.66 |
Day 10 |
0.60 |
0 |
0.60 |
0.60 |
0 |
0.60 |
1.20 |
0.20 |
1.40 |
1.33 |
0.67 |
2.00 |
Day 11 |
0.60 |
0 |
0.60 |
0.40 |
0 |
0.40 |
0.80 |
0.20 |
1.00 |
1.00 |
0.33 |
1.33 |
Day 12 |
0.60 |
0 |
0.60 |
0.40 |
0 |
0.40 |
0.80 |
0.20 |
1.00 |
1.00 |
0 |
1.00 |
Day 13 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
0.80 |
0 |
0.80 |
1.00 |
0 |
1.00 |
Day 14 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
1.00 |
0 |
1.00 |
Day 15 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
1.00 |
0 |
1.00 |
Day 16 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
1.00 |
0 |
1.00 |
Day 17 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
1.00 |
0 |
1.00 |
Day 18 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
1.00 |
0 |
1.00 |
Day 19 |
0.40 |
0 |
0.40 |
0.40 |
0 |
0.40 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Day 20 |
0.60 |
0 |
0.60 |
0.40 |
0.20 |
0.60 |
0.40 |
0 |
0.40 |
1.00 |
0 |
1.00 |
Termination |
0.80 |
0 |
0.80 |
0.40 |
0.40 |
0.80 |
0.60 |
0 |
0.60 |
- |
- |
- |
Summary of dermal reactions (females)
3 mg/kg bw/d |
10 mg/kg bw/d |
50 mg/kg bw/d |
250 mg/kg bw/d |
|||||||||
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
Erythema |
Oedema |
Total |
|
Day 0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Day 4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
Day 5 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
0.20 |
0 |
0.20 |
1.00 |
0.20 |
1.20 |
Day 6 |
0 |
0 |
0 |
0.40 |
0 |
0.40 |
0.40 |
0.40 |
0.80 |
1.00 |
0.80 |
1.80 |
Day 7 |
0 |
0 |
0 |
0.40 |
0 |
0.40 |
0.60 |
0.40 |
1.00 |
1.40 |
1.00 |
2.40 |
Day 8 |
0 |
0 |
0 |
0.20 |
0 |
0.20 |
0.80 |
0.40 |
1.20 |
1.20 |
0.60 |
1.80 |
Day 9 |
0.20 |
0 |
0.20 |
0.20 |
0 |
0.20 |
0.60 |
0.40 |
1.00 |
1.00 |
0.40 |
1.40 |
Day 10 |
0.20 |
0 |
0.20 |
0.20 |
0 |
0.20 |
0.60 |
0.40 |
1.00 |
1.00 |
0.40 |
1.40 |
Day 11 |
0.20 |
0 |
0.20 |
0.40 |
0 |
0.40 |
0.60 |
0.40 |
1.00 |
1.20 |
0.20 |
1.40 |
Day 12 |
0.40 |
0 |
0.40 |
0.60 |
0 |
0.60 |
0.80 |
0.40 |
1.20 |
1.20 |
0.20 |
1.40 |
Day 13 |
0.80 |
0.20 |
1.00 |
1.00 |
0.60 |
1.60 |
0.80 |
0.40 |
1.20 |
1.20 |
0.20 |
1.40 |
Day 14 |
1.00 |
0.60 |
1.60 |
1.20 |
0.60 |
1.80 |
0.80 |
0.20 |
1.00 |
1.20 |
0.20 |
1.40 |
Day 15 |
0.80 |
0.60 |
1.40 |
1.20 |
0.60 |
1.80 |
0.80 |
0.20 |
1.00 |
1.00 |
0 |
1.00 |
Day 16 |
0.80 |
0 |
0.80 |
1.20 |
0.40 |
1.60 |
0.80 |
0 |
0.80 |
1.00 |
0 |
1.00 |
Day 17 |
0.60 |
0 |
0.60 |
1.20 |
0.20 |
1.40 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Day 18 |
0.60 |
0 |
0.60 |
1.00 |
0.20 |
1.20 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Day 19 |
0.60 |
0 |
0.60 |
1.00 |
0.20 |
1.20 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Day 20 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Termination |
0.40 |
0 |
0.40 |
0.80 |
0 |
0.80 |
0.60 |
0 |
0.60 |
1.00 |
0 |
1.00 |
Bodyweights and weight gains
|
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
50 mg/kg bw/d |
250 mg/kg bw/d |
Males |
|||||
Day 0 |
(5) 2.482 |
(5) 2.471 |
(5) 2.503 |
(5) 2.439 |
(5) 2.448 |
Day 7 |
(5) 2.616 |
(5) 2.611 |
(5) 2.710 |
(5) 2.599 |
(5) 2.456 |
Day 14 |
(5) 2.783 |
(5) 2.744 |
(5) 2.810 |
(5) 2.695 |
(2) 2.493 |
Day 20 |
(5) 2.915 |
(5) 2.831 |
(5) 2.938 |
(5) 2.764 |
(2) 2.302 |
Body Weight Gains |
|||||
Day 7 |
(5) 0.134 |
(5) 0.140 |
(5) 0.208 |
(5) 0.160 |
(5) 0.007 |
Day 14 |
(5) 0.301 |
(5) 0.273 |
(5) 0.307 |
(5) 0.256 |
(2) 0.176 |
Day20 |
(5) 0.433 |
(5) 0.360 |
(5) 0.436 |
(5) 0.325 |
(2) -0.115* |
Females |
|||||
Day 0 |
(5) 2.522 |
(5) 2.482 |
(5) 2.583 |
(5) 2.437 |
(5) 2.531 |
Day 7 |
(5) 2.578 |
(5) 2.590 |
(5) 2.678 |
(5) 2.642 |
(5) 2.685 |
Day 14 |
(5) 2.773 |
(5) 2.744 |
(5) 2.787 |
(5) 2.808 |
(5) 2.623 |
Day 20 |
(5) 2.882 |
(5) 2.865 |
(5) 2.901 |
(5) 2.864 |
(3) 2.695 |
Body Weight Gains |
|||||
Day 7 |
(5) 0.056 |
(5) 0.108 |
(5) 0.095 |
(5) 0.204 |
(5) 0.154 |
Day 14 |
(5) 0.251 |
(5) 0.262 |
(5) 0.203 |
(5) 0.370 |
(5) 0.093 |
Day 20 |
(5) 0.360 |
(5) 0.383 |
(5) 0.317 |
(5) 0.427 |
(3) 0.200 |
*significantly differerent to controls (p<0.05)
Cholinesterase activity
|
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
50 mg/kg bw/d |
250 mg/kg bw/d |
|
Males |
||||||
Erythrocyte |
Before treatment |
916.28 |
811.80 |
993.39 |
954.04 |
891.61 |
2h after |
1274.98 |
1020.21 |
687.90** |
646.96** |
- |
|
24h after |
1198.76 |
829.02 |
1049.14 |
500.65** |
- |
|
Plasma |
Before treatment |
257.60 |
325.01 |
280.94 |
284.41 |
298.18 |
2h after |
355.72 |
357.27 |
317.66 |
218.58 |
- |
|
24h after |
385.30 |
386.07 |
323.55 |
232.73* |
- |
|
Brain |
|
11204.60 |
10057.80 |
8904.40 |
7127.60** |
- |
Females |
||||||
Erythrocyte |
Before treatment |
917.69 |
874.41 |
741.74 |
780.84 |
896.69 |
2h after |
1291.47 |
1349.59 |
630.33* |
377.49** |
222.36** |
|
24h after a) |
1135.52 |
1063.48 |
761.98 |
400.29** |
237.47** |
|
Plasma |
before treatment |
139.52 |
139.92 |
161.46 |
124.95 |
127.03 |
2h after |
360.55 |
309.10 |
259.03 |
95.36** |
38.05** |
|
24h after |
356.89 |
325.72 |
212.25** |
143.90** |
22.98** |
|
Brain |
|
12798.00 |
11736.20 |
10119.40* |
9010.20** |
2590.00** |
*significantly different to controls (p<0.05); **p<0.01
Adrenal weights
Week 4 |
0 mg/kg bw/d |
3 mg/kg bw/d |
10 mg/kg bw/d |
50 mg/kg bw/d |
250 mg/kg bw/d |
Males |
|||||
Body weight (kg) |
2.788 |
2.765 |
2.814 |
2.667 |
- |
Adrenal absolute weight (g) |
0.21 |
0.25 |
0.24 |
0.20 |
- |
Adrenal relative weight (%) |
0.07 |
0.09 |
0.08 |
0.08 |
- |
Females |
|||||
Body weight (kg) |
2.808 |
2.681 |
2.817 |
2.768 |
2.641 |
Adrenal absolute weight (g) |
0.21 |
0.20 |
0.25 |
0.22 |
0.28* |
Adrenal relative weight (%) |
0.07 |
0.08 |
0.09 |
0.08 |
11 |
*significantly different to controls (p<0.05)
Applicant's summary and conclusion
- Conclusions:
- A NOAEL could not be determined for this study due to local dermal reactions at the application site in rabbits of all treated groups. A NOAEL for systemic toxicity of 3 mg/kg bw/d can be determined based on the significant inhibition of cholinesterase activity at higher dose levels.
- Executive summary:
The repeated dose dermal toxicity of fenitrothion was investigated in a 21 -day study in the rabbit. Fenitrothion was administered percutaneously to groups of 5 male and 5 female New Zealand White rabbits at the dose levels of 0, 3, 10, 50 and 250 mg/kg bw/d by the topical route for a period of 21 successive days. The test material, a brown oily substance, was administered undiluted. The control group received distilled water. Parameters evaluated included clinical observations (twice daily), dermal reactions (daily), body weights and food consumption (weekly), plasma and erythrocyte cholinesterase activity (one week before treatment, 2 and 24 hours after final dosing) and haematology, biochemistry, brain cholinesterase activity, necropsy, organ weights and histopathology at study termination. Five males and two females at 250 mg/kg bw/d showed deterioration of general condition and died during the administration period (two males and one female were killed in a moribund condition). Signs observed in animals prior to death were hypoactivity, muscular hypotonia, tremor, bradypnoea, hypothermia, salivation, clonic convulsion, loose or mucous stool, diarrhoea and soiled perineum. In the surviving three females at 250 mg/kg bw/d, one animal revealed loose stool and soiled perineum and the other two animals showed no abnormalities. No clinical signs were noted in animals of the control and 3, 10 and 50 mg/kg bw/d groups. Very slight or well defined erythema and very slight or slight oedema were observed at the application site in males and females of the 3, 10 and 50 mg/kg bw/d groups, and were classified as mild according to the Draize index. Males and females of the 250 mg/kg bw/d group showed slightly more severe irritation than other treated groups. The maximum mean irritation scores at 250 mg/kg bw/d were classified as moderate according to the Draize index. The other dermal reaction observed in all groups treated with fenitrothion was desquamation of the epidermis. Depression of body weight gain and decrease in body weights were observed in males and females at 250 mg/kg bw/d. Increased WBC count and variable differential counts were observed in decedents at 250 mg/kg bw/d. No haematological effects were reported at lower dose levels. Increased AST and ALT activity and blood urea nitrogen and a decrease in serum electrolytes were observed in some animals at 250 mg/kg bw/d. No effects on clinical chemistry parameters were reported at lower dose levels. Gross necropsy did not reveal any effects of treatment. Increased adrenal weight was seen in some rabbits at 250 mg/kg bw/d. At 250 mg/kg bw/d, one male and one female revealed slight focal necrosis in the liver; histopathological changes in the digestive tract and kidney were considered to reflect a general deterioration of condition. Erythrocyte cholinesterase activity decreased in males and females at 10, 50 and 250 mg/kg bw/d. Plasma and brain cholinesterase activities decreased in males at 50 and 250 mg/kg bw/d and in females at 10, 50 and 250 mg/kg bw/d. No significant changes in erythrocyte, plasma or brain cholinesterase activities were observed at 3 mg/kg bw/d. A NOAEL could not be determined for this study due to local dermal reactions at the application site in rabbits of all treated groups. A NOAEL for systemic toxicity of 3 mg/kg bw/d can be determined based on the significant inhibition of cholinesterase activity at higher dose levels.
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